Genetic variations in dopamine and inhibitory control: lack of influence on action restraint

Failures of inhibitory control can severely affect everyday life in healthy individuals and represent a common feature of many neuropsychiatric conditions, particularly disorders with dopaminergic disturbances implicated. This study's aim was to examine the interacting influences of three common and functional gene variants that influence dopaminergic pathways on an aspect of inhibitory control (action restraint). Three hundred and twenty two healthy adults were selected from an international consortium linked to Brain Research and Integrative Neuroscience (BRAINnet). DNA was extracted from cheek swab samples and participants were genotyped for the Val158Met single nucleotide polymorphism on COMT (rs 4680), C957T on DRD2 (rs 6277) and the 40bp variable number of tandem repeat on the DAT1 (SLC6A3, 10/10 vs 9+). Response inhibition was measured using a computerised Go/No-Go task. Main effects and interactions between genotypes were explored. We did not observe a genotype effect on fundamental measures of response inhibition, i.e. reaction time (RT) and commission errors. RT variability was significantly increased in DRD2 C957T heterozygotes. In conclusion, this large, non-clinical study reveals that the selected genetic polymorphisms regulating dopamine (COMT, DRD2 and DAT1) do not influence one aspect of response inhibition, action restraint, as measured by the Go/No-Go task, reinforcing the neuropharmacological dissociation between stop-signal and Go/No-Go tasks. Genetic variation in striatal dopamine may, however, contribute to intraindividual RT variability.